The overall goal of this project is to develop models of, and computational strategies for analyzing, the dynamics of interacting closed-loop physiological systems; in particular, the project focuses on elucidating the complex interactions between respiratory control and the control of sleep-wake state. In the past year, we continued to develop a minimal model for delineating the chemoreflex-mediated changes from state-induced fluctuations in respiratory drive. We found that approximately 19% of the respiratory variability in obstructive sleep apneics (OSA) during CPAP (continuous positive airway pressure) therapy could be attributed to chemoreflex-mediated fluctuations in drive. Thus, contrary to expectations, this chemoreflex contribution is not significantly smaller than the 25% found in normals. The estimated chemoreflex loop gain in both groups was not statistically different; however, the characteristic time for the chemoreflex-mediated responses in OSA was only ~60% as long as that for normals. These results suggest that ventilatory stability in OSA subjects is reduced relative to normal controls, and support the hypothesis that respiratory control instability may be a key factor in the pathogenesis of OSA. We also developed an improved methodology for assessing autonomic function in patients with OSA. This methodology is based on two new indices computed from spectral measures of respiration and heart rate variability: the modified ratio of low-frequency to high-frequency power (MLHR) and the average gain relating respiration to RR changes (GRSA). Significant changes resulted in MLHR and GRSA during acute application of CPAP in OSA patients, while no changes in more traditional measures of autonomic function were detectable. We applied spectral analysis and system identification techniques to data obtained from cocaine-exposed and control full-term neonates at two weeks of age during quiet sleep (QS) and active sleep (AS). The cocaine-exposed neonates showed enhanced heart rate variability that was due to an increase in spectral power across all frequency bands during QS, but only in the low-and mid-frequency power bands in AS. The dynamic relationship between respiration and heart rate showed no statistically significant differences between the subject groups or between states. However, a significant interaction effect (P<0.03) between group and state was found. These results suggest an increase in both sympathetic and parasympathetic modulation of heart rate in cocaine-exposed infants.